Hepatitis is a disease of the liver, which is usually caused by viral infections. A significant number of patients suffering from hepatitis are infected with either hepatitis B virus (HBV) or hepatitis C virus (HCV). HCV is an RNA virus with a virion size of 30-60 nm. HBV is a DNA virus with a virion size of 42 nm (D. S. Chen, J. Formos. Med. Assoc., 95(1):6-12 (1996)). Serious complications of hepatitis can include cirrhosis, hepatic failure, liver cancer and death.
As of 1997, nearly 14 million people in the United States and 100 million worldwide were infected with the hepatitis C virus (Alter, M. J., Hepatology, 26(1):625-655 (1997)). It is expected that worldwide, the number of patients has increased to 170 million people in 2002 (ViroPharma Inc. Press Release, Jun. 19, 2002).
Chronic hepatitis C is the most common cause of chronic liver disease and is the leading indication for liver transplantation in the United States (Detre, et al., Viral Hepatitis Rev., 2:219-228 (1996)).
In Egypt, HCV represents the highest donor infection rates recorded so far where 14-24% of blood donors are anti-HCV positive (Hipps, et al., Infect. Dis. 168:789-790 (1993)).
Hepatitis B is a major health problem worldwide, particularly in Asia and Africa. Approximately 300 million people are chronically infected with HBV worldwide and more than one million carriers of HBV are found in the United States. HBV carriers not only become long-term reservoirs of the virus, but also may develop chronic liver disease and have a greatly increased risk of developing liver cirrhosis and cancer.
Unfortunately, there are few effective treatments for hepatitis. Treatment of HCV with recombinant-alpha interferon has a limited long-term efficacy with a response rate of only about 25% (D. S. Chen, J. Formos. Med. Assoc., 95(1):6-12 (1996)). A long-term relapse rate of 24% was reported in Chinese patients with chronic hepatitis B who underwent interferon therapy (Lok, et al., Gastroenterology, 105(6):1833-1838 (1993)). Furthermore, interferon is associated with a number of adverse side effects, including thrombocytopenia, leucopenia, bacterial infections, and influenza-like symptoms. Other agents used in the treatment of hepatitis include the nucleoside analog ribavirin and ursodeoxycholic acid. However, neither has been shown to be particularly effective (D. C. Dale and D. D. Federman, eds. Medicine Sc. Amer., Inc., New York, 4(8):1-8 (1995)). The most effective treatment now in wide spread use may be the combination of Interferon and Ribavirin. (McHutchison et at New England Journal of Medicine, Vol 339, pps. 1485-1491.
The use of herbal therapy and folk medicines has been known for thousands of years in China. In fact, records on the use of herbs date back to biblical times. However, only recently have scientists begun exploring the possible role for herbs in treatment of viral infections. For example, extracts of Hemidesmus indicus rhizomes (Family: Asclepiadaceae) have been found to have anti-viral activity against DNA and RNA viruses (Babbar, et al., Ind. J. Exp. Biol., 8:304-312 (1970)). Likewise, extracts from the root of the Ecballium Elaterium have been used to treat HCV and HBV (EP 0793964 and U.S. Pat. No. 5,648,089). While research in the field of herbal medicines has increased, much remains to be learned about the effectiveness of such herbal remedies.
In view of the above, there is a continuing need in the art for alternative options for treating viral infections such as HCV and HBV. Moreover, there is a need in the art for treatment options that provide minimal side effects.
Accordingly, it is an object of the present invention to provide herbal compositions and methods for treating viral infections such as HCV and HBV. Moreover, it is object of the present invention to provide compositions and methods for treatment that incur minimal side effects to the subject. Another object of the invention is to develop a treatment, which involves a minimum of only two herbal elements. This last object is of vital importance to the eventual large-scale commercial use of a herbal treatment. Current United States regulations impose strict manufacturing controls on the manufacture if pharmaceutical products. Herbal treatments based upon too many herbal component compound manufacturing processes and may make these more complicated treatments commercially impracticable.
The inventors have previously developed a treatment for both Hepatitis C and Hepatitis B, along with other virus caused diseases. The prior attempts involved many different herbs. Some were thought to be anti-viral and some had the purpose of reducing or eliminating side effects. Each treatment had at least ten herbs or extracts from herbs. After a study of United States Federal Drug Administration proposed regulations, the inventors sought to come up with a treatment in which only one or two herbs or extracts from herbs would be used.
One of the extracts was from the herb, Ecballium Elaterium. This herb had long been used to treat liver disease such as jaundice. (See, “Medicinal Plants of North Africa”, Loutfy Boulos, Reference Publications, Inc 1983) Ecballium Elaterium could not be used directly as it has some serious toxicity problems.
See A Manual of Materia Medica and Pharmacology by David M. R. Culbreth, Ph. G., M.D. (1927) which describes the properties of Ecbalium Elaterium as follows: “PROPERTIES—Hydragogue cathartic (most powerful known), producing profuse watery evacuations with griping and much prostration; large doses nauseate, vomit, inflame stomach and bowels, increase flow of urine, and may kill. Does neither vomit nor purge dogs, rabbits, but kills them by convulsions. Those working in it often have ulcerated fingers, eyes, etc”.
Initially the inventors obtained an extract of Ecbalium elaterium preparing herbal drops made by using the fruit of Ecbalium elaterium and washing the fruit with clean water. Approximately a half-kilogram of fruit and one liter of distilled water were combined in an ordinary household electrical grinder. The fruit was ground for two minutes. The mixture was then poured through a sieve of cotton gauze to separate out the larger fruit particles. The mixture was then filtered using Wattmann filter paper. The filtrate (i.e., cell sap) was stored in a refrigerator at 10° C. for approximately 5-7 hours to promote the precipitation of microparticles. The filtrate was then filtered using ceramic sterilization candles to remove any microorganisms. The pH was adjusted to approximately 6.8-7 using dilute sulfuric acid and sodium bicarbonate. A preservative (thiomersal) was added to the sterilized filtrate to provide a concentration of 0.001 gm/liter. The herbal solution was then placed into 10 cc. dropper bottles under aseptic conditions and stored in the refrigerator at about 4 degrees C. The final concentration of the extract was approximately 0.5 weight % cell sap based on the amount of cell sap dissolved in water (5 gms/1000 ml).
This method did produce a successful anti-viral but those treated with Ecbalium elaterium did require additional herbs to minimize side effects. As a result, the treatment had too many herbs, making its future manufacture unfeasible.
The inventors noticed that after placing aluminum foil over the Ecbalium elaterium mixture (in order to protect it from dust) a brown residue would form on the foil. They then isolated the residue and reduced it to liquid form so as to be administered in drops. The inventors surmised that the Ecbalium evaporate might contain an anti-viral and additionally might not contain the toxic part of Ecbalium elaterium. They thought that the evaporate was present at 40 degrees C., as this was roughly the summer temperature in which the Ecbalium elaterium was stored and the discoloring of the covering aluminum occurred. After discarding the use of water, methyl alcohol, and ethyl alcohol, the inventors tried methylene chloride. Methylene chloride is not soluble in water, has mild polarity, and boiling point of 30 to 32 degrees C.
The inventors add the same volume of the solvent, methylene chloride, and the yield-differentiated distillation (using tap water and fresh Ecbalium fruit), then hand shaking for about five minutes in a separating funnel, then leaving the mixture for 30 minutes. This last step gives the solvent a chance for the solvent to be separated form the water due to the different densities. The solvent, which contained the Ecbalium elaterium residue, is then transferred to a rotary evaporation machine. The machine evaporates the solvent away at 29 to 30 degrees C., under vacuum. This process yields about a half milliliter of residue over a period of 3 to 4 hours. The residue is a strong smelling brown oily substance.
A HPLC machine analyzed the above final residue. The result was the largest indication of absorption at 8.648 AU (Angstrom) but the substance remains chemically unidentified. The mechanism of action may be similar to that found by others in extract from Aloe Vera. (See U.S. Pat. No. 5,118,673 Carpenter, et al. Jun. 2, 1992 Uses of aloe products)
The inventors, using their wide experience in herbal therapy, surmised that the herb Camel thorn (Alhagi pseudalhagi), with its long record of versatility, would be a good candidate to test as an anti-viral. Their trial dose of Camel thorn (Alhagi pseudalhagi) in powder form was one teaspoon-full twice a day before meals. They subsequently prepared the single herb in the form of drops by steam distillation process by boiling 0.5 kg of cleaned shoots in 2 liter of tap water thereby gaining 500 ml of a mixture of distilled water and vapor materials. Then, the drops are packed into 10-ml plastic vials. The dose of single herb Camel thorn (Alhagi pseudalhagi) drops is 4 drops nasally once a day.
Since it was known that a combination of ingredients can be more effective in treating Hepatitis C (see Interferon Alfa-2b Alone or in combination with Ribavirin as Initial Treatment for Chronic Hepatitis C, McHutchison et al, New England Journal of Medicine, Vol 339, p 1485-1491, Nov. 19, 1998), the inventors tested both the herbs Alhagi pseudalhagi and Ecballium elaterium residue both singly and in combination.